This is a morphological, biochemical and genetic study of heritable defects in collagen fibrillogenesis resulting in fragile hyperextensible connective tissues. Electron microscopic studies of dogs, cats and sheep with fragile hyperextensible skin have shown that these clinical signs are consistently associated with defects in the fibrillogenesis of dermal collagen. Genetic studies have shown that in both dogs and cats the collagen packing defects and fragile, hyperextensible skin are inherited as a simple autosomal dominant trait. These studies also suggested that the homozygous state of this defect is lethal during the period of embryonic organogenesis, but fragile hyperextensible skin is the only clinical sign in heterozyogous cats. In both the propositi and affected heterozygotes the dermis consisted of a mixture of normal and abnoral collagen fibers. This pattern of inheritance suggested that this defect is due to a defective gene that determines the primary structure of (1) a collagen polypeptide chain or (2) a protein that regulates the packing of collagen molecules into fibrils and fibers. Therefore, pairs of affected and unaffected sibling animals are being used for biochemical, electron microscopic and immunofluorescence studies of collagen and fibronectin in the skin. This includes studies of the synthesis, processing, relatve amounts and structure of the different collagen polypeptide chains in the skin, as well as studies of the collagen binding protein fibronectin in pairs of affected and unaffected animals.